This application relates to a method and composition for use in the treatment of apathy-amotivation syndrome (also known as abulia or anergia syndrome) in neuropsychiatric disorders.
The syndrome of apathy is defined as absence of or decrease in motivation (Marin, Differential Diagnosis and Classification of Apathy, American Journal of Psychiatry 147: 22-30,, January 1990). Slowness of thinking and diminished ability to shift from one set of thinking to the other. This can occur in a variety of apparently unrelated neuropsychiatric disorders. Some of the most common conditions that result in apathy-amotivation syndrome are: schizophrenia, Parkinson's disease, Alzheimer's disease, multiple sclerosis, Huntington's chorea and frontal lobe lesions. (Marin, Apathy: A Neuropsychiatric Syndrome, Journal of Neuropsychiatry and Clinical Neurosciences, 3: 243-254, 1991). In each case apathy-amotivation is just one of a plurality of symptoms associated with the disease. In the past, treatments of other aspects of these conditions such as motor and sensory deficits, dementia, and depression have little or no benefit with respect to apathy-amotivation syndrome.
There is large body of evidence that describe apathy-amotivation syndrome and its manifestation in neuropsychiatric disorders. (Starkstein, et al., Reliability, Validity, and Clinical Correlates of Apathy in Parkinson's Disease, Journal of Neuropsychiatry, Volume 4, Number 2, Spring 1992; Bozzola, et al., Personality Changes in Alzheimer's Disease, Arch Neurol, Volume 49, March 1992; Burns, et al., Clinical Assessment of Irritability, Aggression, and Apathy in Huntington and Alzheimer Disease, The Journal of Nervous and Mental Disease Vol. 178, No. 1; Mendez, et al., Neurobehavioral changes associated with caudate lesions, Neurology 39, March 1989; Robinson, et al., Mood Disorders in Stroke Patients, Brain (1984); House, et al., Mood Disorders in the Year after First Stroke, British Journal of Psychiatry (1991); Benson, et al., Psychiatric Aspects of Neurological Disease, Personality Changes With Frontal and Temporal Lobe Lesions, Grune & Stratton, Inc., 1975; Cummings, Clinical Neuropsychiatry, Grune & Stratton, Inc., 1985; McHugh, et al., Psychiatric Aspects of Neurological Disease, Psychiatric Syndromes of Huntington's Chorea: A Clinical and Phenomenologic Study, Grune & Stratton, 1975; Caine, et al., Psychiatric Syndromes in Huntington's Disease, Am J Psychiatry 140:6, June 1983; Ho, et al., The Acquired Immunodeficiency Syndrome (AIDS) Dementia Complex, Annals of Internal Medicine, Volume III, Number 5, Sep. 1, 1989; Cohen, et al., Amantadine Treatment of Fatigue Associated With Multiple Sclerosis, Arch Neurol Vol. 46, June 1989). The common scientific view is to ascribe apathy-amotivation to deficits in the function of the frontal lobes. (Hecaen, et al., Psychiatric Aspects of Neurological Disease, Disorders of Mental Functioning Related to Frontal Lobe Pathology, Grune & Stratton, 1975; Trimble, Psychopathology of Frontal Lobe Syndromes, Seminars in Neurology, Volume 10, No. 3, September 1990; Strub, Frontal Lobe Syndrome in a Patient With Bilateral Globus Pallidus Lesions, Arch Neurol, Vol. 46, September 1989). In recent years, studies have implicated other brain structures that may be involved in the production of the apathy-amotivation syndrome (e.g., striatum and hippocampal formation) (Wang, Neurobehavioral Chanaes Following Caudate Infarct: A Case Report with Literature Review, Chin Med J (Taipei), 1991; Hedreen, et al., Neuronol loss in layers V and VI of cerebral cortex in Huntington's disease, Neuroscience Letters, 133 (1991); Alvarez, et al., The role of histamine in the anterior hypothalamus and its functional interaction with the hippocampal on exploratory behavior in adult male rats, Behavioural Brain Research, 48: 127-33, 1992) but their specific contribution is yet to be elucidated.
Recently, I have established that apathy-amotivation associated with schizophrenia and Parkinson's disease can be treated using histamine H.sub.2 -antagonists. It is the object of the present invention to extend this same treatment regimen to patients having apathy-amotivation syndrome associated with other neuropsychiatric disorders.